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Genetic toxicity in vitro

No studies on the genotoxicity of the test substance were available; therefore data of studies from structural analogues, conducted according to OECD Guideline 471 (Bacterial Reverse Mutation Test), OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test), and OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test) were used for read-across.

An in vitro Mammalian Cell Gene Mutation Test was conducted with 2,2-bis[[(1-oxopentyl)oxy]methyl]propane-1,3-diyl divalerate (CAS No. 15834-04-5) according to OECD Guideline 476. Mouse lymphoma L5178Y cells were dosed with 0.03, 0.1, 0.3, 1, 3, 10, 33, 100 µg/ml with and without metabolic activation. No signs of toxicity were observed, DMSO was used as vehicle, precipitation was observed at and above 100 µg/ml. There was no significant increase in the number of forward mutations at the thymidine kinase locus of L5178Y mouse lymphoma cells treated with the test material, indicated by the total number of colonies per plate (RA-S, CAS 15834-04-5, Key, Verspeek-Rip, 2010, gene mut in mamm cells, RL2).

In an Ames test conducted with a structural analogue, Decanoic acid, ester with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol octanoate (CAS No. 11138-60-6), Salmonella typhimurium strains TA 1535, TA 1537, TA 1538, TA 98, TA 100 and E.coli WP2 uvr A were treated according to OECD Guideline 471 (RA-S, CAS 11138-60-6, Key, Exxon, Baily, 1996, Ames, RL2).

The test substance was diluted in ethanol and test substance concentrations of 0, 10, 33, 100, 333 and 1000 µg/plate were tested in triplicate, both with and without the addition of a rat liver homogenate metabolising system (S9). Precipitation of the test substance was observed at and above 100 µg/plate. The test material caused no cytotoxicity up to the highest, precipitating dose. No significant increases in the frequency of revertant colonies were recorded for any of the bacterial strains, with any dose of the test material, either with or without metabolic activation.

An in vitro mammalian chromosome aberration test was performed with CAS No. 131459-39-7 (3,5,5-trimethylhexanoic acid mixed tetraesters with PE and valeric acid) in human lymphocytes (RA-S, CAS 131459-39-7, Key, Croda, Wright, 1999, ChrAb, human, RL2). The occurrence of chromosome aberrations was investigated in the presence and absence of metabolic activation (rat liver S9-mix) with test substance concentrations of 0, 312.5, 625, 1250, 2500, 5000 µg/mL diluted with acetone. The test substance did not induce a significant increase in the number of metaphases with aberrations at any preparation time and dose level. No relevant cytotoxic effects were reported. Precipitation of the test substance was observed at and above 1250 µg/ml. Positive controls significantly increased the rate of chromosome aberrations indicating the sensitivity of the assay. In conclusion, the test substance did not induce chromosome aberrations in human lymphocytes, neither in the presence nor in the absence of a metabolic activation system, under these experimental conditions.

  

Genetic toxicity in vivo

No in vivo studies on the genotoxicity of the test substance were available.Fatty acids, C5-10, esters with pentaerythritol (CAS No. 68424-31-7) were found to be not genotoxic in the micronucleus assay in vivo after intraperitoneal application. A single intraperitoneal injection was given to groups of 5 male and 5 female mice at a dose level of 5000 mg/kg bw. Bone marrow samples were taken 24 and 48 hours after dosing.

No statistically or biologically significant increases in the incidence of micronucleated polychromatic erythrocytes over the vehicle control values were seen in either sex at either of the sampling times.

Comparison of the percentage of polychromatic erythrocytes showed no significant differences between the female animals treated with the vehicle control or with the test material. A small, but significant decrease was, however, noted in male mice treated with the test material at 5000 mg/kg bw. This small decrease is, however, considered not to be biologically significant compared to the concurrent control values.

The positive control induced statistically significant and biologically meaningful increases in micronucleated polychromatic erythrocytes, compared to the vehicle control values, thus demonstrating the sensitivity of the test system to a known clastogen(RA-S, CAS No. 68424 -31 -7, Key, Croda, Griffiths, 1992, CTL/P/3792, Micronuc., RL2).

Considering the clearly negative results of the in vitro and in vivo experiments used as read-across and the proven physiological metabolism of fatty acids and excretion of polyols, it can be assumed that fatty acids, C5-9, esters with pentaerythritol (CAS No. 68424-30-6) are not genotoxic, neither in vitro nor in vivo.


Short description of key information:
Genetic toxicity in vitro
RA-S, CAS 11138-60-6, Key, Exxon, Baily, 1996, Ames, RL2 – not mutagenic
RA-S, CAS 131459-39-7, Key, Croda, Wright, 1999, ChrAb, human, RL2 – not clastogenic
RA-S, CAS 15834-04-5, Key, Verspeek-Rip, 2010, gene mut in mamm cells, RL2 – not mutagenic

Genetic toxicity in vivo
RA-S, CAS 68424-31-7, Key, Croda, Griffiths, 1992, CTL/P/3792, Micronuc., RL2 - not genotoxic

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

According to the DSD and CLP criteria for classification and labelling of dangerous substances the CAS No. 68424-30-6 (Fatty acids, C5-9, esters with pentaerythritol) is not classified as mutagenic.